Sertraline hydrochloride, (1S-cis)-4-(3,4 dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine hydrochloride, having the formula
is approved, under the trademark Zoloft®, by the U.S. Food and Drug Administration, for the treatment of depression, obsessive-compulsive disorder and panic disorder.
U.S. Pat. No. 4,536,518 (“the '518 patent”) describes the preparation of sertraline hydrochloride with a melting point of 243-245° C. by treating an ethyl acetate/ether solution of the free base with gaseous hydrogen chloride. The solid state properties of the sertraline hydrochloride so produced are not otherwise disclosed.
U.S. Pat. No. 5,734,083 describes the preparation of a form of sertraline hydrochloride denominated polymorph “T1.”
According to U.S. Pat. No. 5,248,699 (“the '699 patent”), the sertraline hydrochloride produced by the method of the '518 patent has a crystalline form denominated “Form II.” The '699 patent discloses four other polymorphs of sertraline hydrochloride designated Forms I, III, IV, and V, and characterizes them by single crystal x-ray analysis, powder x-ray diffraction, infra-red spectroscopy, and differential scanning calorimetry. The '699 patent reports that Form II is produced by rapid crystallization of sertraline hydrochloride from an organic solvent, including isopropyl alcohol, ethyl acetate or hexane, and generally describes methods for making sertraline hydrochloride Forms I-V. According to this patent, the preferential formation of Forms I, II or IV in an acidic solution consisting of isopropyl alcohol, hexane, acetone, methyl isobutyl ketone, glacial acetic acid or, preferably, ethyl acetate, depends on the rapidity of crystallization. The only method described in this patent for making Forms II and IV is by the rapid crystallization of sertraline hydrochloride from an organic solvent such as those listed above.
The experimental procedure for the preparation of sertraline hydrochloride described in the '518 patent, was repeated in the laboratory. According to the '699 patent, the '518 procedure produces sertraline hydrochloride Form II. Four experiments were performed according to the description in the '518 patent. By following the procedures described in the '699 patent for preparation of sertraline hydrochloride Form II, we were unable to obtain sertraline hydrochloride Form II. Thus there remains a need for reproducible methods for the preparation of sertraline hydrochloride Form II.